6dimethylaminomethyl-1-phenyl-cyclohexane compounds as pharmaceutical active ingredients
This invention relates to 6-dimethylaminomethyl-1-phenyl-cyclohexane compounds, to methods of preparing them and to the use of these compounds in drugs.
The treatment of chronic and non-chronic pain conditions is of great importance in medicine. There is currently a world-wide need for additional pain therapy which is not exclusively opioid but which exhibits good efficacy. The pressing requirement for a target-oriented treatment of chronic and non-chronic pain conditions which is right for the patient, which is to be understood as the successful and satisfactory treatment of pain for the patients, is documented in the large number of scientific works which have recently appeared in the field of applied analgesics or on basic research on nociception.
Opioids have been used for many years for the treatment of pain, even though they give rise to a series of side effects, for example dependency, respiratory depression, gastrointestinal inhibition effects and obstipation. They can therefore only be given over an extended period of time or in high dosages subject to special precautions, for example special prescription regulations (Goodman, Gilman "The Pharmaceutical Basis of Therapeutics" Pergamon Press, New York, 1990).
Tramadol hydrochloride--(1RS,2RS)-2[(dimethylamino) methyl]-1-(3 -methoxyphenyl)cyclohexanol hydrochloride--assumes a special position amongst centrally acting analgesics, since this active ingredient acts as a strong inhibitor of pain without the side effects which are known for opioids (J. Pharmacol. Exp. Ther. 267, 331 (1993)). Tramadol is a racemate and consists of equal amounts of (+) and (-) enantiomers. In vivo, this active ingredient forms the metabolite O-desmethyl-tramadol, which likewise exists as a mixture of enantiomers. Investigations have shown that both the enantiomers of tramadol and the enantiomers of the tramadol metabolite have a part in the analgesic effect (J. Pharmacol. Exp. Ther. 260, 275 (1992)).
Compounds of formula ##STR1##
are known from Chem. Pharm. Bull. 32, 2279 (1984) in which Z represents H or OH These substances have an analgesic effect which is considerably weaker than that of tramadol.